A Study to Assess the Efficacy and Safety of MNK-1411 in Duchenne Muscular Dystrophy

Muscular Dystrophy, Duchenne Clinical Trial

— BRAVE  

Official title:

A Multicenter, Randomized, Parallel Group, Double Blind, Multiple Dose, Placebo Controlled Study to Assess the Efficacy and Safety of MNK-1411 in Male Participants 4 to 8 Years of Age With Duchenne Muscular Dystrophy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03400852
• Other study ID #: MNK14112096
• Secondary ID: 2017-004139-35
• Status: Terminated
• Phase: Phase 2
• Start date: July 27, 2018
• Est. completion date: February 25, 2020

Study information

• Verified date: February 2021
• Source: Mallinckrodt
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, double blind, placebo controlled, multiple dose study to examine the safety and efficacy of MNK-1411 in male subjects 4 to 8 years of age (inclusive) with Duchenne Muscular Dystrophy (DMD).

Description:

The main purpose of this study is to determine the effect of MNK-1411 on motor function in participants with Duchenne Muscular Dystrophy (DMD). Information is collected only from caretakers who are fluent in English, using the Pediatric Outcomes Data Collection Instrument (PODCI). The PODCI is a validated 86-question instrument completed by the parent or legal guardian of children 2 to 10 years of age to assess a variety of health outcome measures (Uzark et al, 2012). This study will only collect information for the PODCI domains of sports and physical functioning and transfer/basic mobility.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 44
• Est. completion date: February 25, 2020
• Est. primary completion date: February 25, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 4 Years to 8 Years

Eligibility

Inclusion Criteria:

1. Participants must have a documented diagnosis of Duchenne Muscular Dystrophy (DMD) confirmed by complete dystrophin deficiency (by immunofluorescence and/or immunoblot), or identifiable mutation in the DMD gene where reading frame can be predicated as "out of frame," or complete dystrophin gene sequencing consistent with DMD; AND in the opinion of the Investigator, a typical clinical profile consistent with DMD.

2. Participants taking approved treatments for DMD (by a Health Authority) that target dystrophin gene mutations (e.g., eteplirsen or ataluren) may be enrolled in the study if they have been on a stable dose for 30 days prior to the first dose of study drug, and plan to remain on that dose throughout the study.

Exclusion Criteria:

1. Participant has had previous systemic treatment with corticosteroids within 2 months prior to the Screening Visit. Exception: In subjects who were down-titrated to a physiological dose of corticosteroids (ie, 3mg/m2 of prednisone or deflazacort) a maximum of 1 month of no greater than a physiological dose followed by 1 month completely off corticosteroids prior to the Screening Visit will be acceptable for study entry. Transient previous use of corticosteroids will be evaluated on a case-by-case basis by the sponsor or designee. The use of topical or intra-articular corticosteroids is permitted during the study

2. Participant is unable to complete the 10 meter Walk/Run test at the Screening and/or Baseline Visit.

3. Participant has Type 1 or Type 2 diabetes mellitus.

4. Participant has a history of chronic active hepatitis including acute or chronic hepatitis B, or acute or chronic hepatitis C.

5. Participant has a history of tuberculosis (TB) infection, any signs/symptoms of TB, or any close contact with an individual with an active TB infection.

6. Participant has known immune compromised status (not related to disease/condition under study), including but not limited to, individuals who have undergone organ transplantation or who are known to be positive for the human immunodeficiency virus.

Related Conditions & MeSH terms

• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• MNK-1411
MNK-1411 (1 mg/mL suspension) for subcutaneous injection

Other:
• Placebo
Placebo suspension for subcutaneous injection

Locations

Country	Name	City	State
Bulgaria	University Multiprofile Hospital for Active Treatment Aleksandrovska EAD	Sofia
Israel	Edith Wolfson Medical Center	H_olon
Italy	Ospedale San Raffaele S.r.l. - PPDS	Milano	Lombardia
Mexico	Neurociencias Estudios Clinicos S.C.	Culiacán	Sinaloa
Mexico	Instituto de Investigaciones Aplicadas a la Neurociencia A.C.	Durango
Mexico	Hospital Civil Fray Antonio Alcalde	Guadalajara	Jalisco
Serbia	Clinic of Neurology and Psychiatry for Children and Youth	Belgrade
Spain	Hospital de La Santa Creu i Sant Pau	Barcelona
Spain	Hospital Sant Joan de Deu - PIN	Esplugues De Llobregat
Spain	Hospital Universitari i Politecnic La Fe Valencia	Valencia
Turkey	Mersin Universitesi Tip Fakultesi Hastanesi	Mersin
United States	Rare Disease Research, LLC	Atlanta	Georgia
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	NW FL Clinical Research Group, LLC	Gulf Breeze	Florida
United States	Monroe Carell Jr Childrens Hospital at Vanderbilt	Nashville	Tennessee
United States	UT Health Science Center, San Antonio	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Mallinckrodt ARD LLC

Countries where clinical trial is conducted

United States,  Bulgaria,  Israel,  Italy,  Mexico,  Serbia,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Complete 10 Meter Walk/Run[	10 Meter Walk/Run is a motor function test to measure the functional capability in patients with DMD.	Baseline, Week 24
Secondary	North Star Ambulatory Assessment (NSAA) Score	The NSAA is comprised of 17 items, each of which is graded using the standard scorecard. Each assessment is rated as 0 - unable to achieve independently, 1 - modified method but achieves goal independent of physical assistance from another, or 2 - normal with no obvious modification of activity. The subscale scores are summed for a total score ranging from 0 to 34. The higher the total score, the better the outcome.	Baseline, Week 24
Secondary	Time to Climb 4 Standardized Stairs	Time to Climb 4 Standardized Stairs is a motor performance test	Baseline, Week 24
Secondary	Time to Stand From a Supine Position	Time to stand from a supine position is a motor function test to measure the functional capability in subjects with DMD.	Baseline, Week 24
Secondary	Quantitative Muscle Testing Scores at Baseline	Quantitative muscle testing measured strength-knee flexion and extension measured in Newtons, using a dynamometer	Baseline
Secondary	Quantitative Muscle Testing Scores at Week 24	Quantitative muscle testing measured strength-knee flexion and extension measured in Newtons, using a dynamometer	Week 24
Secondary	Summary of Adverse Events in the Blinded Treatment Period	Clinically significant changes in vital signs, height, weight, immunogenicity and laboratory assessments were reported as adverse events (AEs)	within 28 weeks
Secondary	Summary of Adverse Events in the Open Label Period	Clinically significant changes in vital signs, height, weight, immunogenicity and laboratory assessments were reported as adverse events (AEs)	within 28 weeks